Mitomycin C-dextran conjugate: a novel high molecular weight pro-drug of mitomycin C

Abstract

A high molecular weight derivative of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D) has been synthesized and its biological and pharmacological properties investigated. MMC is released from MMC-D in vitro with a half-life of 24 h. After intraperitoneal injection of MMC-D, free MMC could be detected in plasma and urine of mouse for 5–8 h, while MMC administered as a free form was eliminated rapidly. After MMC-D, given to mice bearing Ehrlich ascites carcinoma or B16 melanoma there was a reduction in toxicity and an increase in survival time compared with MMC. These observations suggest that the high molecular weight MMC-dextran derivative is a kind of pro-drug which persists in the body giving a sustained release of free MMC thus significantly increasing the antitumour activity of the parent drug.